This application represents a renewal application of the Dana Farber Harvard Cancer Center (DF/HCC) Prostate Cancer SPORE. The application involves basic, translational and clinical investigators from several Harvard Institutions including the Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Dana Farber Cancer Institute, Harvard School of Public Health and the Massachusetts General Hospital. It also involves investigators from the Broad Institute, a genomics institute formed through a collaboration between Harvard Medical School and the Massachusetts Institute of Technology. Five Projects will be supported in this application including 1) Molecular Signatures of Lethal and Indolent Prostate Cancer 2) Genetic and Clinical Characterization of the 8q24 Prostate Cancer Risk Locus 3) Development of Kinase Inhibitor Combination Therapy in Prostate Cancer 4) Modulating Transcription Factor Targets via Chemical Genomics 5) Androgen Signaling in Hormone Refractory Disease. These projects will be supported by three cores 1) Administration, evaluation and planning 2) Biostatistics and Computational Biology 3) Tissue and Pathology. We also include Developmental Projects and Career Development Programs. The overall goal of the DF/HCC SPORE is the translation of biological and technological advances into clinically meaningful advances for men with prostate cancer.